Analysis of the Anatomical and F unctional onditions using

160 Pages·2012·3.48 MB·English

by  Ana Catarino

UUNNIIVVEERRSSIIDDAADDEE DDEE LLIISSBBOOAA
FACULDADE DE CIÊNCIAS
Departamento de Física

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basis of AAuuttiissmm SSppeeccttrruumm CCoonnddiittiioonnss using
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Elleeccttrrooeenncceepphhaallooggrraapphhyy

AAnnaa MMaarriiaa FFeerrrreeiirraa PPaarraaddeellaa CCaattaarriinnoo

DOOUUTTOORRAAMMEENNTTOO EEMM ENGENHARIA BIOMÉDICA E BIOFÍSICA
2012

UUNNIIVVEERRSSIIDDAADDEE DDEE LLIISSBBOOAA
FACULDADE DE CIÊNCIAS
Departamento de Física

AAAnnnaaalllyyysssiiisss ooofff ttthhheee AAAnnnaaatttooommmiiicccaaalll aaannnddd FFFuuunnnccctttiiiooonnnaaalll
bbbaaasssiiisss ooofff AAAuuutttiiisssmmm SSSpppeeeccctttrrruuummm CCCooonnndddiiitttiiiooonnnsss using
MMMaaagggnnneeetttiiiccc RRReeesssooonnnaaannnccceee IIImmmaaagggiiinnnggg aaannnddd
EElleeccttrrooeenncceepphhaallooggrraapphhyy

AAnnaa MMaarriiaa FFeerrrreeiirraa PPaarraaddeellaa CCaattaarriinnoo

Thesis supervised by:
Professor Doutor Alexandre Andrade
IInnssttiittuuttoo ddee BBiiooffííssiiccaa ee EEnnggeennhhaarriiaa BBiioomméédica
FFaaccuullddaaddee ddee CCiiêências, Universidade de Lisboa

DOOUUTTOORRAAMMEENTO EM ENGENHARIA BIOMÉDICA E BIOFÍSICA
2012

CONTENTS

LIST OF FIGURES ................................................................................................................................ v
LIST OF TABLES ................................................................................................................................. vii
LIST OF ABBREVIATIONS ...................................................................................................................... ix
ABSTRACT......................................................................................................................................... xi
RESUMO ........................................................................................................................................ xiii
PUBLICATIONS ................................................................................................................................ xvii
ACKNOWLEDGEMENTS ...................................................................................................................... xix
1. GENERAL INTRODUCTION ........................................................................................................... 1
1.1. AUTISM SPECTRUM CONDITIONS ......................................................................................... 1
1.1.1. MECHANISM AND CAUSES .......................................................................................... 2
1.2. MAGNETIC RESONANCE IMAGING ........................................................................................ 4
1.2.1. PHYSICAL PRINCIPLES ................................................................................................. 4
1.2.2. ECHOES .................................................................................................................... 9
1.2.3. SPATIAL ENCODING .................................................................................................. 11
1.2.4. FUNCTIONAL MRI ................................................................................................... 15
1.3. ELECTROENCEPHALOGRAPHY ............................................................................................. 18
1.3.1. BRAIN ANATOMY AND PHYSIOLOGY ........................................................................... 18
1.3.2. EEG RECORDING ..................................................................................................... 21
LIMITATIONS ....................................................................................................................... 22
TYPICAL ACTIVITY ................................................................................................................. 23
1.3.3. SIGNAL ANALYSIS ..................................................................................................... 24
FREQUENCY AND POWER ANALYSIS ......................................................................................... 24
EVENT RELATED POTENTIALS .................................................................................................. 25
NON-LINEAR, COMPLEXITY AND CONNECTIVITY ANALYSIS OF THE EEG SIGNAL ................................ 26
i
MULTISCALE ENTROPY ...................................................................................................... 27
WAVELET TRANSFORM COHERENCE .................................................................................... 28
1.3.4. APPLICATIONS OF EEG IN RESEARCH .......................................................................... 28
2. AN MRI INVESTIGATION OF ATYPICAL CORTICAL THICKNESS IN AUTISM SPECTRUM CONDITIONS ........ 31
2.1. INTRODUCTION ............................................................................................................... 31
2.1.1. AIMS OF THE STUDY ................................................................................................. 32
2.2. METHODS ...................................................................................................................... 32
2.2.1. PARTICIPANTS ......................................................................................................... 32
2.2.2. MRI ACQUISITION ................................................................................................... 35
2.2.3. CORTICAL SURFACE RECONSTRUCTION ........................................................................ 35
2.2.4. STATISTICAL ANALYSIS .............................................................................................. 36
2.3. RESULTS ......................................................................................................................... 37
2.3.1. VARIATION OF KERNEL WIDTH ................................................................................... 37
2.3.2. CORTICAL THICKNESS ............................................................................................... 37
2.3.3. AGE-CORTICAL THICKNESS CORRELATION .................................................................... 39
2.4. DISCUSSION .................................................................................................................... 40
3. AN fMRI INVESTIGATION OF DETECTION OF SEMANTIC INCONGRUITIES IN AUTISM SPECTRUM
CONDITIONS ................................................................................................................................... 43
3.1. INTRODUCTION ............................................................................................................... 43
3.1.1. ASC AND SEMANTIC INCONGRUITIES .......................................................................... 43
3.1.2. EEG AND fMRI IN THE STUDY OF SEMANTIC INCONGRUITIES ......................................... 43
3.1.3. AIMS OF THE STUDY ................................................................................................. 44
3.2. METHODS ...................................................................................................................... 44
3.2.1. PARTICIPANTS ......................................................................................................... 44
3.2.2. MRI ACQUISITION ................................................................................................... 45
3.2.3. fMRI TASK ............................................................................................................. 45
3.2.4. DATA ANALYSIS ....................................................................................................... 47
3.3. RESULTS ......................................................................................................................... 52
ii
3.3.1. BEHAVIOURAL PERFORMANCE ................................................................................... 52
3.3.2. fMRI FUNCTIONAL ACTIVATION – WITHIN-GROUP CONTRASTS....................................... 53
3.3.3. fMRI FUNCTIONAL ACTIVATION – BETWEEN-GROUP CONTRASTS .................................... 58
3.4. DISCUSSION .................................................................................................................... 59
4. ATYPICAL EEG COMPLEXITY IN AUTISM SPECTRUM CONDITIONS: .................................................. 65
A MULTISCALE ENTROPY ANALYSIS ..................................................................................................... 65
4.1. INTRODUCTION ............................................................................................................... 65
4.1.1. ASC AND FACE PROCESSING ...................................................................................... 65
4.1.2. BRAIN COMPLEXITY IN ASC ....................................................................................... 66
4.1.3. AIMS OF THE STUDY ................................................................................................. 67
4.2. METHODS ...................................................................................................................... 68
4.2.1. PARTICIPANTS ......................................................................................................... 68
4.2.2. EEG RECORDING ..................................................................................................... 69
4.2.3. SIGNAL ANALYSIS ..................................................................................................... 70
4.2.4. MULTISCALE ENTROPY.............................................................................................. 71
4.2.5. POWER ANALYSIS .................................................................................................... 72
4.2.6. STATISTICAL ANALYSIS .............................................................................................. 73
4.3. RESULTS ......................................................................................................................... 74
4.3.1. BEHAVIOURAL PERFORMANCE ................................................................................... 74
4.3.2. MSE ANALYSIS ........................................................................................................ 74
4.3.3. POWER ANALYSIS .................................................................................................... 78
4.4. DISCUSSION .................................................................................................................... 78
5. INTERHEMISPHERIC FUNCTIONAL CONNECTIVITY IN AUTISM SPECTRUM CONDITIONS: AN EEG STUDY
USING WAVELET COHERENCE TRANSFORM ......................................................................................... 83
5.1. INTRODUCTION ............................................................................................................... 83
5.1.1. COHERENCE AND CONNECTIVITY ................................................................................ 83
5.1.2. COHERENCE AND CONNECTIVITY IN ASC ..................................................................... 84
5.1.3. AIMS OF THE STUDY ................................................................................................. 86
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5.2. METHODS ...................................................................................................................... 86
5.2.1. PARTICIPANTS ......................................................................................................... 86
5.2.2. EEG RECORDING ..................................................................................................... 87
5.2.3. SIGNAL ANALYSIS ..................................................................................................... 87
5.2.4. WAVELET TRANSFORM COHERENCE ........................................................................... 88
5.2.5. STATISTICAL ANALYSIS .............................................................................................. 91
5.3. RESULTS ......................................................................................................................... 92
5.3.1. BEHAVIOURAL PERFORMANCE ................................................................................... 92
5.3.2. WTC ANALYSIS ....................................................................................................... 92
5.4. DISCUSSION .................................................................................................................. 100
6. GENERAL DISCUSSION ............................................................................................................ 107
6.1. UNIFYING MODELS OF ASC ............................................................................................. 107
6.1.1. ATYPICAL NEURAL CONNECTIVITY IN ASC .................................................................. 108
6.1.2. LIMITATIONS OF THE DATASETS USED IN THIS THESIS ................................................... 109
6.2. fMRI MEASURES OF CONNECTIVITY IN ASC ....................................................................... 110
6.2.1. LIMITATIONS ON THE INTERPRETATION OF THE fMRI STUDY DESCRIBED IN CHAPTER 3 .... 112
6.3. EEG MEASURES OF CONNECTIVITY IN ASC ........................................................................ 112
6.4. ANATOMICAL MEASURES OF CONNECTIVITY IN ASC ............................................................ 114
6.5. LIMITATIONS OF THE CONNECTIVITY THEORY IN ASC AND FUTURE PERSPECTIVES .................... 115
6.6. CONCLUSIONS ............................................................................................................... 116
REFERENCES ................................................................................................................................. 118

iv
LIST OF FIGURES

Figure 1.1 – The protons’ magnetic moments align parallel or anti-parallel in the presence of
an external field (a) and differences in energy states generate a positive net magnetization, in
the same direction as the main field (b). ...................................................................................... 5
Figure 1.2 – When an RF pulse is applied, the net magnetization is flipped by an angle α. . 6
(cid:1)(cid:2)
Figure 1.3 – The rotating frame of reference, rotating at the Larmor frequency; the RF
magnetic pulse and magnetization vector will appear to be stationary. ........................ 6
(cid:3)(cid:4) (cid:1)(cid:2)
Figure 1.4 – Transverse magnetization decay, due to spin-spin interactions. ............................. 7
Figure 1.5 – Decay of transverse magnetization M due to spin-spin interactions and field
xy
inhomogeneities. ........................................................................................................................... 8
Figure 1.6 – Recovery of longitudinal magnetization M due to spin-lattice interactions. .......... 8
z
Figure 1.7 – (a) T1-weighted image of the brain, showing cerebrospinal fluid in dark, brain
matter in mid-gray and adipose (fat) tissue in bright tones; (b) T2-weighted image of the brain
showing cerebrospinal fluid as very bright and brain and other types of tissue in mid-gray. ...... 9
Figure 1.8 – Gradient echo sequence ......................................................................................... 10
Figure 1.9 - Spin echo sequence ................................................................................................. 11
Figure 1.10 – Gradients in the x, y and z axis are used for spatial encoding; ............................. 13
Figure 1.11 – Spin-echo (SE) imaging sequence ......................................................................... 14
Figure 1.12 – Gradient echo based echo planar imaging (GE-EPI) sequence ............................. 15
Figure 1.13 – Blood Oxygen Level Dependent (BOLD) response to neural activity. ................... 16
Figure 1.14 – Diagram of brain anatomy showing the corpus callosum, cerebral cortex, brain
stem and cerebellum, as well as the functionally segregated lobes. ......................................... 19
Figure 1.15 – Diagram of a neuron’s resting potential. .............................................................. 19
Figure 1.16 – Neuron’s structure and stimulus propagation diagram ........................................ 20
Figure 1.17 – Action potential being generated and propagated along the axon of a neuron (a)
and a diagram illustrating a referential montage (b). ................................................................. 21
Figure 1.18 – Placement of electrodes on the scalp according to the International 10-20
system. ........................................................................................................................................ 22
Figure 1.19 – Example of an EEG power graph. .......................................................................... 25
Figure 1.20 – Averaging procedure in EEG data to extract ERP waveform. ............................... 26
Figure 2.1 – Boxplot representations of the age distribution for both Control and ASC groups.
..................................................................................................................................................... 37
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